Methods and formulations for treating sialic acid deficiencies

Abstract

Extended release formulations, methods of making, and methods of use, for example, in treatment of sialic acid deficiencies.

I claim: 
     
       1. An extended release pharmaceutical formulation in oral unit dosage form comprising
 about 43.3% w/w of N-acetylneuraminic acid (NeuAc) or a pharmaceutically acceptable salt thereof; 
 about 25.5% w/w of hypromellose or about 25.5% w/w of polyethylene oxide; 
 about 21.2% w/w of sodium alginate; and 
 about 4.2% w/w of carrageenan; 
 wherein the in vitro dissolution release profile of the formulation at intestinal pH is near linear, and the formulation contains about 325 mg to about 500 mg of NeuAc in each unit dosage and provides a steady plasma concentration of NeuAc upon three or four times of oral administration in 24 hours. 
 
     
     
       2. The extended release pharmaceutical formulation of  claim 1 , further comprising about 1% to about 10% of a mixture of microcrystalline cellulose and colloidal silicon dioxide. 
     
     
       3. The extended release pharmaceutical formulation of  claim 1 , further comprising about 0.1% to about 1% of one or more lubricants. 
     
     
       4. The extended release pharmaceutical formulation of  claim 3 , wherein the one or more lubricants comprise magnesium stearate. 
     
     
       5. The extended release pharmaceutical formulation of  claim 1 , comprising
 about 43.3% w/w of N-acetylneuraminic acid (NeuAc) or a pharmaceutically acceptable salt thereof; 
 about 25.5% w/w hypromellose; 
 about 4.2% w/w carrageenan; and 
 about 21.2% w/w sodium alginate. 
 
     
     
       6. The extended release pharmaceutical formulation of  claim 5 , further comprising
 about 1% to about 10% w/w of the mixture of microcrystalline cellulose and colloidal silicon dioxide; and 
 about 0.1% to about 1% w/w magnesium stearate. 
 
     
     
       7. The extended release pharmaceutical formulation of  claim 1 , comprising
 about 43.3% w/w of N-acetylneuraminic acid (NeuAc) or a pharmaceutically acceptable salt thereof; 
 about 25.5% w/w of polyethylene oxide; 
 about 4.2% w/w carrageenan; and 
 about 21.2% w/w sodium alginate. 
 
     
     
       8. The extended release pharmaceutical formulation of  claim 7 , further comprising
 about 1% to about 10% w/w of the mixture of microcrystalline cellulose and colloidal silicon dioxide; and 
 about 0.1% to about 1% w/w magnesium stearate. 
 
     
     
       9. A method for treating a sialic acid deficiency in an individual in need thereof comprising administering an effective amount of N-acetylneuraminic acid (NeuAc) or a pharmaceutically acceptable salt thereof, in the extended release formulation of  claim 1 . 
     
     
       10. The method of  claim 9 , wherein the sialic acid deficiency is a myopathy associated with sialic acid deficiency. 
     
     
       11. The method of  claim 10 , wherein the myopathy associated with sialic acid deficiency is Hereditary Inclusion Body Myopathy (HIBM), Nonaka myopathy, and/or Distal Myopathy with Rimmed Vacuoles (DMRV). 
     
     
       12. The extended release pharmaceutical formulation of  claim 6 , wherein the unit dosage form is a tablet or capsule.